丁苯酞预处理对大鼠心肺复苏后脑缺血再灌注损伤的保护作用研究  

Protective effect of butylphthalide pretreatment on cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation in rats

作　　者：麦叶 顾勇 MAI Ye;GU Yong(Emergency and Critical Medicine,Hainan Hospital of Traditional Chinese Medicine,Haikou 570000,Hainan Province,China;Department of Encephalopathy,Hainan Hospital of Traditional Chinese Medicine,Haikou 570000,Hainan Province,China;Department of Thoracic Surgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]海南省中医院急危重症医学,海南海口570000 [2]海南省中医院脑病科,海南海口570000 [3]南方医科大学南方医院胸外科,广东广州510515

出　　处：《中国临床药理学杂志》2020年第15期2246-2249,2260,共5页The Chinese Journal of Clinical Pharmacology

基　　金：广东省自然科学基金资助项目(2017A030313622);广东省科技计划课题资助项目(2016A020215113);广东省广州市科技计划课题资助项目(201804010446)。

摘　　要：目的探究丁苯酞预处理对大鼠心肺复苏后脑缺血再灌注损伤的保护作用。方法将大鼠随机分为假手术组、模型组、对照组和低、中、高剂量实验组,每组12只。于大鼠窒息前10 min,低、中、高剂量实验组分别经股静脉注射丁苯酞0.25,0.50和0.75 mg;对照组经股静脉注射1×10^4 U·kg^-1乌司他丁注射液;假手术组和模型组均经股静脉注射等量0.9%NaCl。除假手术组外,其余各组均建立大鼠心肺复苏后脑缺血再灌注损伤模型;假手术组仅进行气管插管及动静脉穿刺。用神经功能缺损评分标准评估大鼠神经功能缺损情况,用Tunel染色观察大鼠脑组织神经细胞凋亡情况,用免疫印迹法检测大鼠脑组织中高迁移率族蛋白1(HMGB-1)、晚期糖基化终产物受体(RAGE)和核因子-κB(NF-κB)蛋白的表达情况。结果低、高剂量实验组和模型组的神经功能缺损评分分别为(42.06±3.75),(55.51±5.24)和(32.52±4.51)分,脑组织神经细胞凋亡率分别为(27.72±1.73)%,(18.17±2.46)%和(38.47±2.47)%,HMGB-1分别为(0.78±0.09),(0.41±0.06)和(0.90±0.15),RAGE分别为(0.81±0.13),(0.61±0.08)和(1.12±0.16),核NF-κB分别为(1.52±0.13),(0.78±0.06)和(2.06±0.19),质NF-κB蛋白分别为(0.13±0.04),(0.26±0.04)和(0.09±0.02),低、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论丁苯酞预处理对心肺复苏后脑缺血再灌注损伤具有保护作用,其可能是通过抑制HMGB-1/RAGE/NF-κB通路,降低脑神经细胞凋亡来实现。Objective To investigate the protective effect of butylphthalide pretreatment on cerebral ischemia-reperfusion injury in rats after cardiopulmonary resuscitation.Methods The rats were randomly divided into sham-operation group,model group,control group and experimental-L,-M,-H groups with 12 cases per group.Ten minutes before asphyxiation in rats,the experimental-L,-M,-H groups were given butylphthalide 0.25,0.50 and 0.75 mg,transfemoral vein injection;the control group received 1×10^4 U·kg^-1 ulinastatin,transfemoral vein injection;the sham-operation and model groups were treated with the same amount of 0.9% NaCl,transfemoral vein injection.Except the sham-operation group,the other groups were established models of cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation in rats;the sham-operation group was only subjected to tracheal intubation and arteriovenous puncture.The neurological deficit was assessed by the neurological deficit score.TUNEL staining was used to observe the apoptosis of neurons in brain tissue of rats.Western Blot was used to detect the expression of high mobility group box-1(HMGB-1),receptor for advanced glycation end products(RAGE),nuclear factor kappa B(NF-κB).Results The neurological deficit scores of the rats in the experimental-L,-H groups and model group were(42.06±3.75),(55.51±5.24)and(32.52±4.51),the neuronal apoptosis rates of brain tissue were(27.72±1.73)%,(18.17±2.46)%and(38.47±2.47)%,HMGB-1 were(0.78±0.09),(0.41±0.06)and(0.90±0.15),RAGE were(0.81±0.13),(0.61±0.08)and(1.12±0.16),the nuclear NF-κB were(1.52±0.13),(0.78±0.06)and(2.06±0.19),the cytoplasm NF-κB proteins were(0.13±0.04),(0.26±0.04)and(0.09±0.02).There were significant differences in the above-mentioned indexes between the experimental-L,-H groups and the model group(all P<0.05).Conclusion Butylphthalide pretreatment has a protective effect on cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation,which may be through inhibiting HMGB-1/RAGE/NF-κB pathway and r

关 键 词：丁苯酞 心肺复苏 高迁移率族蛋白1 晚期糖基化终产物 核因子-ΚB 

分 类 号：R972[医药卫生—药品]